Identification of an inducible factor secreted by pancreatic cancer cell lines that stimulates the production of fucosylated haptoglobin in hepatoma cells.
Fucosylation is one of the most important oligosaccharide modifications and is involved in cancer and inflammation. Recently, fucosylated haptoglobin was identified as a possible tumor marker for pancreatic cancer. The molecular mechanism underlying increases in fucosylated haptoglobin in sera of patients with pancreatic cancer seems to be complicated. Our previous study [N. Okuyama, Y. Ide, M. Nakano, T. Nakagawa, K. Yamanaka, K. Moriwaki, K. Murata, H. Ohigashi, S. Yokoyama, H. Eguchi, O. Ishikawa, T. Ito, M. Kato, A. Kasahara, S. Kawano, J. Gu, N. Taniguchi, E. Miyoshi, Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation, Int. J. Cancer 118 (11) (2006) 2803-2808] demonstrated that pancreatic cancer cells secrete a factor, which induces the production of haptoglobin in hepatoma cells. In the present study, we found that interleukin 6 (IL6) expressed in pancreatic cancer is a factor that induces the haptoglobin production, using a neutralizing antibody for IL6. Real-time PCR analyses revealed the up-regulation of fucosylation regulatory genes after IL6 treatment, resulting increases in fucosylated haptoglobin being revealed by a lectin ELISA. This pathway could be one of the possible mechanisms underlying increases in haptoglobin in sera of patients with pancreatic cancer.
Narisada
Megumi
M
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan.
Kawamoto
Sayuri
S
Kuwamoto
Kana
K
Moriwaki
Kenta
K
Nakagawa
Tsutomu
T
Matsumoto
Hitoshi
H
Asahi
Michio
M
Koyama
Nobuto
N
Miyoshi
Eiji
E
D000906:Antibodies / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics; D015870:Gene Expression; D006242:Haptoglobins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D000093242:Interleukin-6 Inhibitors
D000906:Antibodies; D017077:Culture Media, Conditioned; D005643:Fucose; D005647:Fucosyltransferases; D006242:Haptoglobins; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C485359:HP protein, human